title: The Groucho protein Grg4 suppresses Smad7 to activate BMP signaling.
abstract: Groucho related genes encode transcriptional repressor proteins critical for normal developmental processes. The bone morphogenetic proteins belong to the transforming growth factor-β (TGF-β) superfamily and play important signaling roles in development and disease. However, the regulation of BMP signaling, especially within cells, is largely unknown. In this report, we show that expression of the Groucho related gene Grg4 robustly activates the expression of a BMP reporter gene, as well as enhancing and sustaining the upregulation of the endogenous Id1 gene induced by BMP7. BMP7 administration did not affect the endogenous level of Grg4 nor did it enhance the phosphorylation of receptor activated Smad proteins. Rather, Grg4 expression reduced the levels of the endogenous inhibitory Smad7, thus increasing the transcriptional responses mediated by BMP responsive sequences. The data point to a novel mechanisms for attenuating BMP signaling through altering the ratio of activating versus inhibitory Smad proteins.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Dressler
mesh_terms: D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*; D013489:Suppression, Genetic
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D009687:Nuclear Proteins; D012097:Repressor Proteins; C497806:SMAD7 protein, human; D051906:Smad7 Protein; C465817:TLE4 protein, human
keywords: BMP; BMP Response element; BMP signaling; BRE; EGFP; Grg4; Groucho; Groucho related gene 4; Kidney fibrosis; PRC2; Polycomb repressor complex 2; Smad7; TGF; Tle; bone morphogenetic protein; enhanced green fluorescent protein; transducin-like enhancer of split; transforming growth factor